实验性肝损伤大鼠肠道屏障功能障碍研究

Effects of experimental liver injury on the intestinal barrier in rats

目的观察不同程度肝损伤大鼠血浆及肠道组织内毒素、D乳酸、二胺氧化酶的动态变化，探讨肝损伤时肠道机械屏障功能的损伤情况。方法15只大鼠作为正常对照组（A组），15只大鼠作为急性肝损伤组（B组），25只大鼠作为急性肝功能衰竭组（C组），采用分光光度法测定血浆内毒素、D乳酸、二胺氧化酶，回肠组织内毒素及二胺氧化酶水平的动态变化，HE染色及电镜观察肝组织细胞形态和亚细胞的结构变化。组问比较采用单因素方差分析。结果B、C组大鼠血浆D-乳酸活性均明显高于A组，分别为（4．32±1．13）mg／L和（11．62±5．44）mg／L对比（0．77±0．25）mg／L，P〈0．05；血浆二胺氧化酶活性先升高后降低，但均明显高于A组，分别为（0．81±0．26）U／ml和（0．62±0．22）U／ml对比（0．47±0．11）U／ml，P〈0．05；回肠二胺氧化酶活性逐渐降低，B、C两组与A组比较，差异均有统计学意义（P〈0．05）；B组血浆及肠组织内毒素活性与A组相比差异不明显（P〉0．05）；C组则明显高于A、B两组（P〈0．05）。HE染色发现C组存在大片肝细胞坏死，回肠黏膜明显萎缩，部分绒毛断裂、脱落或相互融合,上皮细胞变性、坏死、脱落。电镜观察可见肠黏膜微绒毛稀疏脱落，细胞内线粒体肿胀。结论D乳酸和二胺氧化酶在肝损伤早期即可以明显升高，是检测肠黏膜屏障功能的敏感指标，内毒素血症是肝损伤加重的重要因素。

Objective To study the effects of experimental liver injury on the intestinal barrier, and to evaluate the significance of plasma D（-）-lactate, diamine oxidase （DAO） and endotoxin in live injury. Methods Fifty-five rats were randomized into the acute liver failure group （group C, n = 25）, acute liver injury group （group B, n = 15）, and control group （group A, n = 15）. The concentrations of D（-）-lactate, DAO and endotoxin in plasma were detected by spectrophotograph. The morphology and subcellular structure were observed under optical microscope and transmission electron microscope. Results Acute liver failure and acute liver injury models were established successfully. The concentrations of D（-）-lactate and DAO in the plasma of experimental groups （group B and C） were significantly higher than those in the control group （P 〈0.05）; the concentration of intestinal DAO in experimental groups were significantly lower than that in the control group （P 〈 0.05）; the level of endotoxin in C group was significantly higher than that in group A and group B （P 〈 0.05）. Conclusion Liver injury induces hyperpermeability of the rat intestinal mucosal barrier, plasma D（-）-lactate and DAO are sensitive markers for early diagnosis of liver injury, plasma endotoxin may accelerate deterioration of liver function.